Expression profiling and prediction of distant metastases in head and neck squamous cell carcinoma

Abstract

Background: For breast and prostate cancer, a gene expression signature of the tumour is associated with the development of distant metastases. Regarding head and neck squamous cell carcinoma (HNSCC), the only known risk factor is the presence of >3 tumour-positive lymph nodes. Aim: To evaluate whether a HNSCC gene expression signature can discriminate between the patients with and without distant metastases. Methods: Patients with HNSCC with and without distant metastases had .3 tumour-positive lymph nodes, and did not differ with respect to other risk factors. Statistical analysis was carried out using Student's t test, as well as statistical analysis of microarrays (SAM), to assess the false discovery rate for each gene. These analyses were supplemented with a newly developed method that computed deviations from gaussianorder statistics (DEGOS). To validate the platform, normal mucosa of the head and neck was included as control. Results: 2963 genes were differently expressed between HNSCC and normal mucosa (t test; p,0.01). More rigorous statistical analysis with SAM confirmed the differential expression of most genes. The comparison of genes in HNSCC with and without metastases showed 150 differently expressed genes (t test; p,0.01), none of which, however, could be confirmed using SAM or DEGOS. Conclusions: No evidence for a metastasis signature is found, and gene expression profiling of HNSCC has seemingly no value in determining the risk of developing distant metastases. The absence of such a signature can be understood when it is realised that, for HNSCC in contrast with breast cancer, the lymph nodes are a necessary in-between station for haematogenous spread.

Prediction of future metastasis and molecular characterization of head and neck squamous-cell carcinoma based on transcriptome and genome analysis by microarrays

“…In our previous work, we were unable to identify genes that could be used to predict whether the patients would develop distant metastasis following treatment. A related study reached the same conclusion (Braakhuis et al, 2006). The previous unsuccessful studies were of smaller scale, which could account for the inability to find predictor gene models.…”

A Poor Prognosis Subtype of HNSCC Is Consistently Observed across Methylome, Transcriptome, and miRNome Analysis

“…More recently, analysis of 40 HNSCC samples uncovered a 75-gene signature that predicts adverse clinical outcome and that comprises genes linked to EMT, NF-kB signaling, and cell-cell adhesion (27). Comparison of 11 metastasizing (M) with 8 nonmetastasizing (NM) HNSCC found 150 differential-expressed genes but no evidence for a metastasis signature (13). Our 98-tumor sample study (52 NM vs. 46 M) found 614 genes with significantly altered expression that are associated with development, differentiation, adhesion, and motility, and a 4-gene predictor that was able to discriminate NM from M patients with a 77% success rate (14).…”

“…11, 12; see Supplementary Table S1 for a more extensive compilation). Gene expression signatures have been reported that correlate with adverse prognosis and with higher risk for distant metastasis (13)(14)(15). However, these signatures have little in common and need further functional and clinical validation.…”

Actin cytoskeletal mediators of motility and invasion amplified and overexpressed in head and neck cancer

“…Patient outcome directly correlates with the degree of local and regional invasion [2]. Although it has long been recognized that invasive HNSCC is a negative prognostic indicator, the lack of a universal molecular ''metastasis signature'' has hampered the understanding of the signaling pathways that underlie HNSCC invasion and metastasis [3]. While recent advances in screening gene expression arrays have begun to identify candidate genes responsible for regulating motility and invasion in HNSCC [4,5], a comprehensive understanding of the factors contributing to HNSCC invasion is still emerging.…”